One common neurological syndrome, Parkinsonism has been the object of attempts at cell transplant therapy. Bjorklund et al., Brain Res., 177:555-560 (1979); Lindvall et al., Science, 247:574-577 (1990); Freed, Restor. Neurol. Neurosci., 3:109-134 (1991). Parkinsonism is caused by a loss of dopamine-producing neurons in the substantia nigra of the basal ganglia. Burns et al., N. Engl. J. Med., 312:1418-1421 (1985); Wolff et al., Neurobiology, 86:9011-9014 (1989). Parkinson's disease, a disease of unknown etiology which is characterized by the clinical manifestations of Parkinsonism, is caused idiopathic destruction of these dopamine-producing neurons. Parkinsonism may be caused by a variety of drugs, e.g., antipsychotic agents, or chemical agents, e.g., 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. Burns et al., Proc. Natl. Acad. Sci. USA, 80:4546-4550 (1983) and Bankiewicz et al., Life Sci., 39:7-16 (1986).
Attempts have been made to reverse the clinical manifestations of experimentally-induced Parkinsonism by transplanting dopaminergic cells into the striatum of affected animals. Genetically modified fibroblasts (transfected with DNA encoding tyrosine hydroxylase) have been successfully transplanted into animals having lesions of dopaminergic pathways. Motor function and behavior of the animals improved following implantation of the dopamine producing fibroblasts. Wolff et al., Proc. Natl. Acad. Sci. USA, 86:9011-9014 (1989); Fisher et al., Neuron, 6:371-380 (1991). Graft survival may be enhanced, and hence clinical improvement prolonged, by transplantation of fetal tissue, as compared to cells obtained following birth. Gage and Fisher, Neuron, 6:1-12 (1991). Fresh fetal dopaminergic neurons have been transplanted into the caudate nucleus of monkeys following chemical injury to the nigrostriatal dopamine system. Following transplantation, the injury-induced behavioral deficits improved. Bankiewicz et al., J. Neurosurg., 72:231-244 (1990) and Taylor et al., Prog. Brain Res., 82:543-559 (1990). Humans suffering from Parkinsonism have been treated by striatal implantation of dopaminergic neurons. Lindvall et al., Arch. Neurol., 46:615-631 (1989); Widner et al., New Engl. J. Med., 327:1556-1563 (1992). However, these treatments have been hampered by the high rate of cell death that occurs in the transplanted cells. In fact, it is estimated that as little as 5-10% of the cells survive upon transplantation.
Thus, there remains a need to increase the survival of grafted cells, in particular a need to increase the survival of cells used to treat neurological diseases.